Despite their intimidating size and multitude of nasty weapons, macrophages languish without GcMAF “activation.” Quantifying immune activation. Macros use “antigen presenting” messengers to reverse immunosuppression and activate other immune cells. Elevated Nagalase blocks GcMAF-driven macrophage activation, resulting in immunosuppression.
I think you’d have to admit that macrophages are pretty amazing—and intimidating—characters. Expanded to human scale, they would be far superior to any existing weapon. They’d be able to blow their way through cement walls, devour moose-sized animals whole and grab stuff that was fifty feet away with a cluster of their long strong ad hoc arms. But—as with most things that seem too good to be true—there’s a hitch. Despite their incredible potential to protect and defend us, macrophages are naturally indolent. These slackers sleep until noon (figuratively speaking), and hang out in the blood stream like a beach bum at the seashore. It might be more generous to say that in their natural state they are “off duty.” Macros accomplish absolutely nothing beyond eating enough to stay alive, and indulging in the occasional “replication experience.” An inactive (or deactivated) macrophage lacks the killer instinct and might float right past a huge gathering of cancer cells or some partying virus particles, oblivious to their presence. Not exactly a killing machine; more like a gargantuan lifeless blob of cold gooey marshmallow.
To get motivated, these loafers need a swift kick in the butt. Because we are serious scientists, however, we have to call this “macrophage activation.” It is accomplished by specific “activator proteins” that attach to receptors on the macrophage’s surface, not unlike the toe of a boot (the activator protein) being embedded in the butt (the receptor) of a slacker (the macrophage). Though several types of molecules are known to give macros a gentle shove, GcMAF is by far the most potent macrophage activating factor. In fact, nothing comes close.
When GcMAF activates macrophages
As GcMAF docks on its receptors on the outer surface of the macrophage, it sends a signal to the entire cell, telling it to become aggressive, accelerate all activities to warp speed, and prepare for battle. Our laid- back beachcombers morph into frenzied kamikaze warriors. We are not talking about a nudge here; the word “activation” may be too weak to describe a phenomenon that consists of a 30-fold increase in macrophage activity. Imagine a Model T putting along at 20 mph suddenly transforming into a jet plane doing 600!!! You get the idea.
GcMAF activation transforms macrophages—more or less instantaneously (okay, it takes about 3.5 hours)—into a super conqueror that vanquishes cancer cells and virions at a phenomenal rate. GcMAF restores the “tumoricidal capacity” of macrophages—it’s ability to rapidly scarf and kill viruses and cancer cells—that had been obstructed by the Nagalase. Battalions of activated macros now track down and chew their way through enemy armies, spewing out dead parts along the roadside behind them so fast they make it look easy.
Quantifying macrophage activation
Dr. Yamamoto quantified several specific measures of macrophage activation. Comparing deactivated to GcMAF-reactivated macros, he observed a 30-fold increase in rate of tumor cell ingestion (phagocytosis), a 15-fold increase in the “oxidative burst” (a sudden release of superoxide (O2-) ions that zaps cancer cells, bacteria, and viruses), a 40-fold increase in systemic macrophage counts, and an exponential 180-fold rise in macrophage levels in inflamed lesions. (The latter because activated macros, via a process known as chemotaxis—are attracted toward, and migrate, to areas of inflammation—e.g., cancers and viral infections.)
Weekly injections of 100 ng (100 billionths of a gram) unleashes armies with billions of these GcMAF-activated cloned macrophages that relentlessly attack and gradually annihilate small tumors within about six months. (Dr. Yamamoto’s metastatic breast, colon and prostate cancer cases were all put into a five year remission—if not cured—within this time frame.)
Larger tumors—a bigger meal for the macros, so to speak— present more of a challenge. Here, results will certainly vary from one patient to the next, and some will not be curable. We really don’t yet have hard data on larger masses. The macros will certainly do their best—if activated—but for each patient there is going to be a point of no return where the tumor has gotten so big (or the viral load so large) that it can successfully fend off and stay ahead of the best efforts of the activated macros.
Activated macros use “antigen presenting” messengers to reverse immunosuppression
Like that proud mouser cat who insists on dropping dead rodents at his master’s feet to prove he is earning his keep, macrophages, in a strange, microscopic sense, are similarly proud of the fact that they have identified, trapped, phagocytized, killed, and dismembered a desperado, be it cancer cell, bacterium, or viral particle. So, to spread the word of their success to their immune cell comrades, macros release triumphant clouds of messenger molecules.
Macrophages also want to pass on identity information to other immune cells so that everybody else can more easily identify the bad guys. To accomplish this, macros biochemically paint the molecular biological equivalent of a huge luminescent “X” on scraggly pieces of leftover detritus that (prior to dismemberment in its phagolysosome) had been part of a cancer cell or a virus. Once released into the intercellular fluid, these brightly-labeled parts float off like a message in a bottle that, when discovered by another immune cell, tells it to “Keep an eye out for anything resembling this guy—and when you see it, kill it.”
Other immune cells find the bottles, read the messages, and instantaneously know—and remember—that this is the kind of cell they should be targeting. Word spreads fast among phagocytes. Since living cancer cells contain these same parts as those marked with the “X,” lymphocytes, other macrophages, and other immune cells now can instantaneously recognize the enemy and take them out without further ado. We call this “antigen presenting,” and it serves a dual purpose: first it spreads the word about whom to target, and second, it transfers the activation of macros to all other immune cells.
Elevated Nagalase is synonymous with immunosuppression
If macros aren’t activated, antigen-presenting (and all other immune functions) slows to a crawl. Cancers and viral infections deactivate macrophages by manufacturing and releasing Nagalase (alpha-N-acetylgalactosaminidase), the enzyme that prevents GcMAF production.
Without GcMAF (and with Nagalase), the entire immune system has dropped out. They’ve reverted to a collection of stagnant, indolent, ineffectual cells—all “gone fishin’.” The end result is stagnation—general immunosuppression—and an environment in which cancers and viruses get a huge green light.
Deactivated macrophages malfunction in numerous ways. Phagocytic activity dramatically declines. Now no invaders are being eaten, so no luminously labeled tumor or bug parts are being spit out, so ‘antigen presenting’ screeches to a halt.
Without antigen presenting, the rest of the immune system won’t be warned that invaders are nearby, so it remains dormant. As you can see, the deactivation itself perpetuates more deactivation; it’s a vicious cycle. So all the other immune cells sit idly by waiting for marching orders that never come. The entire cascade that leads to ramped up immune activity is blocked when macros are not being activated by GcMAF.
From the macrophage’s perspective, this is a nightmare scenario. Like Gulliver, it has been tied down and immobilized by hordes of Lilliputian Nagalase molecules. Big Mac wants to get up and go out and kick some butt, but it can’t. Immune activity grinds to a halt. Dr. Yamamoto puts it this way: “Macrophages are the major phagocytic and antigen-presenting cells. Because macrophage activation for phagocytosis and antigen presentation to B and T lymphocytes is the first (and) indispensable step in the development of both humoral and cellular immunity, lack of macrophage activation leads to immunosuppression.” (Immunotherapy of Prostate Cancer with GcMAF. Yamamoto et al., Translational Oncology Vol. 1, No. 2, 2008.)